Two days after Obama's election victory, Emanuel was announced as Obama's designee for White House Chief of Staff.[5] He resigned from the House on January 2, 2009, and began his duties as Chief of Staff on January 20, 2009, the day of Obama's inauguration.[5]

On January 27, 2011, the Illinois Supreme Court reversed a lower court's ruling[6] that had cast doubt on Emanuel's candidacy; the court unanimously decided that Emanuel did not abandon his Chicago residency by serving in the White House, thus affirming his ability to run for mayor.[7] He won the Mayoral election on February 22, 2011, with 55% of the vote.[8] President Obama appointed William M. Daley, the brother of Emanuel's predecessor as mayor, as Chief of Staff to replace Emanuel.

Emanuel created a transition team from varied backgrounds.[9][10] On November 16, the city council voted unanimously to adopt the mayor's first budget, which decreased the budget by $34 million and increased spending by $46.2 million, supported by increasing fees and fines. Despite most Aldermen opposing cuts to library workers and the closure of mental health clinics, they ultimately supported it, calling it "honest".[11][12] At a news conference in November 2012, Emanuel listed his top three priorities for the state legislature as security and pension reform, adding a casino to Chicago, and equal marriage rights for same-sex couples.[13] At a press conference with Illinois GovernorPat Quinn, who previously vetoed legislation to put a casino in Chicago, the two were "very close" to reaching a deal.[14]

Emanuel won his second term during the run-off re-election campaign. He defeated Jesus "Chuy" Garcia. Emanuel won 56.76% of the votes.

In November and into December 2015, Emanuel has been criticized for his handling of the Laquan McDonald shooting, mainly for covering and allowing Chicago police to get away with excessive use of force on black minorities. [15]Chicago Tribune columnist John Kass wrote that the Emanuel administration withheld from the public the police dashboard camera video of the Laquan McDonald shooting in order to secure the re-election.[16] Since December 2015, over half of Chicagoans believe that Emanuel should resign with such support from the New York Times, Al Sharpton, Black Lives Matter, U.S senator Bernie Sanders and Illinois governor Bruce Rauner.

While a high school student working part-time at an Arby's restaurant, Emanuel severely cut his right middle finger on a meat slicer, which was later infected from swimming in Lake Michigan. His finger was partially amputated due to the severity of the infection.[17]